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1: Blood. 2002 Apr 1;99(7):2468-76.
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CD4(+) and CD8(+) anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity.

Steinbrink K, Graulich E, Kubsch S, Knop J, Enk AH.

Department of Dermatology, University of Mainz, Langenbeckstrasse 1, D-551312 Mainz, Germany. steinbrink@hautklinik.klinik.uni-mainz.de

Interleukin-10 (IL-10)-treated dendritic cells (DCs) induce an alloantigen- or peptide-specific anergy in various CD4(+) and CD8(+) T-cell populations. In the present study, we analyzed whether these anergic T cells are able to regulate antigen-specific immunity. Coculture experiments revealed that alloantigen-specific anergic CD4(+) and CD8(+) T cells suppressed proliferation of syngeneic T cells in a dose-dependent manner. The same effect was observed when the hemagglutinin-specific CD4(+) T-cell clone HA1.7 or tyrosinase-specific CD8(+) T cells were cocultured with anergic T cells of the same specificity. Anergic T cells did not induce an antigen-independent bystander inhibition. Suppression was dependent on cell-to-cell contact between anergic and responder T cells, required activation by antigen-loaded DCs, and was not mediated by supernatants of anergic T cells. Furthermore, anergic T cells displayed an increased extracellular and intracellular expression of cytotoxic T-lymphocyte antigen (CTLA)-4 molecules, and blocking of the CTLA-4 pathway restored the T-cell proliferation up to 70%, indicating an important role of the CTLA-4 molecule in the suppressor activity of anergic T cells. Taken together, our experiments demonstrate that anergic T cells induced by IL-10-treated DCs are able to suppress activation and function of T cells in an antigen-specific manner. Induction of anergic T cells might be exploited therapeutically for suppression of cellular immune responses in allergic or autoimmune diseases with identified (auto) antigens.

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PMID: 11895781 [PubMed - indexed for MEDLINE]